Mycophenolate Mofitil Identified As Promising Scleroderma-Related Interstitial Lung Disease Treatment

New data recently presented at the 2015 American College of Rheumatology Annual Meeting in San Francisco showed that mycophenolate mofitil is as efficient as cyclophosphamide for the treatment of interstitial lung disease in individuals with scleroderma.

Scleroderma, or systemic sclerosis, is a chronic systemic autoimmune disease characterized by a hardening of the skin that, in its more severe form, can also affect internal organs. One particular clinical complication of scleroderma is interstitial lung disease, a condition characterized by progressive scarring of lung tissue eventually leading to an impaired breathing ability.

“For a sizeable fraction of people with scleroderma, scaring lung disease can be associated with a great deal of suffering and even with death,” explained lead investigator in the study, Philip Clements, MD, MPH, professor emeritus, David Geffen School of Medicine at University of California, Los Angeles in a recent news release. “We postulated that the interstitial lung disease seen in scleroderma was caused in part by inflammation. We therefore sought to decrease the inflammation with medications that have strong anti-inflammatory properties, namely cyclophosphamide and mycophenolate mofitil.”

The research team followed 142 patients with interstitial lung disease associated with scleroderma for two years to assess the effect of oral cyclophosphamide (Cytoxan®) or mycophenolate mofitil (CellCept®) in patients’ forced vital capacity.

All patients enrolled in the study had a scleroderma diagnosis for about seven years and presented difficulty in breathing, moderate shortness of breath, or an initial forced vital capacity result between 45-80%. All patients also had evidence of lung scarring or thickening in high-resolution computed tomography (CT) scans.

For the study, each participant was randomly assigned to orally receive 2 mg/kg of cyclophosphamide daily for a period of one year and then a placebo every day for the second study year. The second group of patients received up to 1,500 mg of mycophenolate mofitil twice per day for the two years of the study. At baseline and every three months until study completion, each patient had a physical examination involving lung function tests, the Modified Rodnan Skin Scoring, and an assessment questionnaire focused on patients’ symptoms.

At two years of follow-up, the results revealed that both groups exhibited identical and significant improvements in skin thickening (modified Rodnan Skin Score), lung function (measured by forced vital capacity), breathlessness (assessed by a breathing questionnaire), and in interstitial lung change on high-resolution CT scan of the lungs.

A total of 56 patients did not finish the two-year study, and of these, 36 patients were from the group receiving cyclophosphamide. 23% of the patients under cyclophosphamide treatment and 4% of the patients under mycophenolate mofitil treatment received an alternative treatment with tocilizimab, rituximab, mycophenolate mofitil or cyclophosphamide, after stopping the study treatment medication.

“Many of the cyclophosphamide dropouts were put on strong anti-inflammatory medications by their primary physicians after they had stopped study medications. We hypothesize that these treatments — that were started outside the study framework — could have artificially improved the outcomes in these cyclophosphamide dropouts at a time when they would have been receiving placebo if they had continued study medication in the second year,” Dr. Clements explained concerning the role alternative treatments might have played in the outcomes of the study.

In terms of side events, the most commonly observed were deficiencies in blood platelets, weight loss and reduction in white blood cell count; however, these were not related with an increase in the cases of pneumonia or excessive bleeding. According to Dr. Clements, although both medications have the potential for serious adverse events, with vigilant monitoring they can be used relatively securely for the treatment of scleroderma patients with lung disease.

“The most frequent cause of death among patients with scleroderma is interstitial lung disease. Since interstitial lung disease produces permanent damage predominantly in the first five-to-seven years of scleroderma, it is important that people with scleroderma get screened with lung function tests regularly every six months in those first five-to-seven years. If a patient’s lung function declines, rheumatologists should consider treating him or her as early as possible with cyclophosphamide or mycophenolate mofitil to try to prevent further progressive lung scaring,” concluded Dr. Clements.